The overall goal of this project is to evaluate changes in vascular function and contractile reactivity in diabetic/hypertensive rats. Focus also includes an evaluation of possible mechanisms underlying these vascular changes. It has been shown that various prostaglandins cause a contraction of isolated blood vessels from hypertensive and all xan-induced diabetic rats. Experiments also have been directed to changes in vascular relaxation characteristics of blood vessels from normal, hypertensive and diabetic rats. Correlation has been made between these various contractile and relaxant effects of various vasoactive substances and their ability to translocate calcium ion. The research will provide crucial information on an important question: Does the presence of a combined diabetic/hypertensive state result in an exacerbation of vascular responses to vasoactive substances which is not seen with either disease state alone? Protocols include treating the hypertensive and diabetic animals with appropriate drugs to normalize their blood pressure and glucose metabolism. These changes will be related to changes in vascular reactivity.